In order to understand the natural history and outcome of patients with AS, this proposal will study multiple[unreadable] ingredients in a model of disease outcome. Any true comprehension of this disease must consider genetic[unreadable] factors, disease activity over time, treatment with new biologic agents, and psychosocial constructs.[unreadable] Outcome is a complex construct as well, taking into account patient reported factors of pain and function[unreadable] loss, accumulated radiographic damage, and morbid events such as hip replacements, etc. Our previous[unreadable] experience in assessing this disease in a cross-sectional manner has led us to approach the question in a[unreadable] model that can quantify and examine each factor for its relative importance to the outcome variables. In[unreadable] order to accomplish this objective, we propose 5 Aims:1) we will recruit and retain 300 additional patients[unreadable] with AS of any disease duration to complement the 600 USA patients already recruited and to retain those[unreadable] already enrolled in the ongoing PSOAS cohort; 2) we will perform an analysis of 675K SNPs as predictors of[unreadable] disease outcome in 1000 UK patients with AS in terms of functional impairment (as measured by the BASFI),[unreadable] disease activity (as measured by the BASDAI) and age at disease onset (disease duration). These 675K[unreadable] SNPs will be identified as predictors for disease susceptibility as part of a genome wide scan in 1000 UK AS[unreadable] patients as performed in project 1, aim 2; 3) we will confirm and extend the observations from Aim 2 in a[unreadable] cohort of 1500 USA AS patients with SNPs derived from the output of Aim 2 in this proposal and from Project[unreadable] 1, Aim 2. In this aim we will identify SNPs that are predictive of functional and radiological outcomes in the[unreadable] large (900 patient) PSOAS cohort of AS patients from North America that either has already been or will be[unreadable] recruited and retained in Aim 1 of this project; 4) we will identify and examine the relationships between[unreadable] psychosocial factors (coping, helplessness, and mood disturbances) and progression of disease in our newly[unreadable] identified cohort (300 subjects) as well as in follow-up intervals of the previously identified PSOAS cohort[unreadable] (400 subjects); 5) we will examine the relative contributions of genetic and all of the other non-genetic factors[unreadable] (addressed in Aims 2-4 above) that contribute to outcome in this cohort using analytic techniques developed[unreadable] in Project 4 of this submission. It is anticipated that non-genetic components of disease outcome and[unreadable] progression (including treatments with biologic agents) will be able to be quantified and examined for their[unreadable] relative importance to patient outcome.